Alzheimer's disease (AD) affects a total of 5.3 million individuals in the U.S. alone, making it the 7th leading cause of death and also costing about 172 billion dollars annually. Currently, AD diagnosis is predominantly based on clinical and psychometric assessment. However, diagnosis can only be certain if an autopsy reports the presence of characteristic neuritic -amyloid plaques and neurofibrilatory tangles in specific brain regions in an individual with a history of progressive dementia. Thus, there is a significant unmet need for non-invasive objective diagnosis and quantification of pathologies, as well as general assessment of disease progression. The goal of this project is to develop a novel neuroimaging analysis framework that will harness the complementary information from different imaging modalities for effective quantification of disease -induced pathologies, so as to promote early detection for possible treatment and prophylaxis. Achieving this goal requires significant innovation in neuroimage analysis techniques to detect sophisticated yet subtle brain alteration patterns. Accordingly, the specific aims of this project are (Aim 1: Disease Diagnosis) to develop a multimodality multivariate diagnosis technique for accurate identification of individuals who are at risk for AD, (Aim 2: Progress Monitoring) to design a novel multi-task kernel learning framework for prediction and quantification of brain abnormality at various disease stages, and (Aim 3: Evaluation) to assess the developed methods using a large database of elderly subjects, for their diagnostic power in quantifying brain alteration patterns in AD/MCI patients, their predictive power of MCI patients who are at risk for AD, and also their capability in quantifying abnormalities as the disease progresses. We expect, upon successful completion of this project, that the resulting comprehensive, integrated, and effective diagnosis/monitoring framework will be conducive to improving the success of early detection of MCI/AD, as well as other neurological disorders including schizophrenia, autism, and multiple sclerosis. Public Health Relevance Statement: Prior to the appearance of clinical symptomatology, AD undergoes a prodromal phase, lasting from years to decades, with disease pathology or predisposition that is clinically undetectable or uncertain. Thus, identifying individuals who are t risk for AD is critical if disease-modifying treatments are to be effective. For this reason, the neuroimage analysis techniques developed in this project are significantly relevant to public health in that they will help improve accuracy in patient identification and disease monitoring for effective treatment.